A procedure was developed for the large-scale purification of EGF receptor from cultured human cells utilizing immunoaffinity chromatography with monoclonal anti-EGF receptor antibodies. Partial amino acid sequence (collaboration with M. Waterfield) analysis of six peptides derived from EGF receptor very closely matched a part of the deduced sequence of the V-erb-B transforming protein of avian erythroblastosis virus (AEV). The complete amino acid sequence of EGF receptor deduced from human cDNA clones (collaboration with A. Ullrich) indicated that V-erb-B protein is a truncated EGF receptor. It is proposed that the virus acquired part of the cellular gene sequence of EGF receptor. This truncated receptor lacked the external binding domain but retained the transmembrane and cytoplasmic domain involved in stimulation of cell proliferation and possesses intrinsic tyrosine kinase activity. Similar proteins are also expressed in leukemias induced by the chronic avian leukosis virus which activates the C-erbB /EGF receptor gene. Approximately one third of brain tumors of glial origin overexpress the EGF receptor and have amplification. Detailed analysis of genomic DNA from these tumors with various cDNA probes of the EGF receptor indicate that in addition to gene amplification the EGF receptor gene is rearranged. Hence, lesions in the gene of EGF receptor are associated with viral neoplasias in birds and also in human cancers. (J)